Methods for external treatment of blood

ABSTRACT

Vascular access systems, devices and methods for facilitating repeated access to a blood vessel. These systems, devices and methods can be used in external blood treatment, such as dialysis, and in intra-venous administration of medicines, such as heparin, for extended periods of time, while avoiding deleterious effects such as those derived from repeated puncturing of the blood vessel tissues or exposure of such tissues to abnormal fluid flows. The vascular access systems comprise an anastomosis graft vessel, an occlusal device, such as an occlusal balloon, and a port device for accessing the occlusal device. Occlusal devices can be self-contained, they can rely on osmosis, and they can serve as the support of an agent to which the blood stream is exposed, either by transport or by mere contact. In addition, occlusal devices can adopt a distended and a collapsed configuration, the latter allowing for blood flow through the anastomosis graft vessel.

BACKGROUND OF THE INVENTION

1. The Field of the Invention

The present invention relates to external treatment of blood. Inparticular, the present invention relates to methods for externallytreating blood without having to repeatedly puncture the blood vesselsbeing accessed.

2. Present State of the Art

Procedures that require the repeated access to blood vessels includedialysis and the delivery of medicines for an extended period of time.The multiple punctures that such repeated access necessitates eventuallyrender the blood vessel unsuitable for further effective injections. Inaddition, some external blood treatment methods rely on the extractionof blood from an artery and on the subsequent injection of the treatedblood into a vein. The characteristics of the fluid flow in an arteryare significantly different from the characteristics in the fluid flowin a vein. These fluid flow dissimilarities may lead to additionaladverse effects that detrimentally affect the long term accessibility ofthe blood vessels that must be accessed for the external blood treatmentto be effectively performed. For example, in an arterio-venous graftconstructed as a vascular access for dialysis, the blood flow and bloodpressure characteristic of the arterial circulation are so differentfrom the blood flow and blood pressure in the vein into which the bloodof the AV graft flows, that the vein usually develops hyperplasia andstenoses.

It is desirable to provide a device that permits multiple access to ablood vessel for the purpose of delivering medicines into the patient'sblood stream in such a way that the receiving blood vessel is not soseverely damaged that it becomes unavailable after a few medicineadministrations.

It is also desirable to provide a device that permits multiple access toa blood vessel for external blood treatment, such as hemodialysis, insuch a way that the blood vessel being accessed does not becomeunavailable for successive dialysis operations.

Furthermore, it would be desirable to provide a device that is suitablefor multiple vascular access for the purpose of long term medicinedelivery into the patient's blood flow and also for the purpose ofeffectively practicing hemodialysis for a long period of time.

The practical advantages of such device would be considerably enhancedif it could be lodged subcutaneously and if it were reliably attachableto a blood vessel by anastomosis techniques. In addition, such vascularaccess device would have to be appropriately configured to allow forcontrolled and selected blood flow through it and to allow for acontrolled delivery of physiologically active agents, such as medicines.It is also desirable to provide methods for performing hemodialysis suchthat blood to be dialyzed can be drawn from a vein and injected intoanother vein once it has been dialyzed, without having to repeatedlypuncture the veins involved in hemodialysis.

These goals should be accomplished while minimizing, or avoiding to themaximum extent possible, undesirable adverse effects such as vesselthrombosis, blood stagnation, the formation of undesirable turbulence,and the formation of blood clots.

The present invention focuses on objectives described hereinbelow forsolving problems which are associated with repeated vascular access, andprovides devices and methods with advantageous features for solving suchproblems.

OBJECTS AND BRIEF SUMMARY OF THE INVENTION

A blood vessel that is repeatedly accessed, and in particular repeatedlypunctured, deteriorates to the point that vascular access becomesincreasingly difficult and eventually impossible. When vascular accessplaces the blood vessel under exceptional fluid dynamics conditions orsubjects the vascular tissues to the deleterious side effects of certainmedications, vascular deterioration can be seriously accelerated. Anexample of such exceptional fluid dynamics conditions is the bloodvolume and pressure that a vein is subjected to when it receives thearterial blood flow from an AV (arterio-venous) graft that has beencreated to provide vascular access for dialysis.

Although an occasional vascular access can be performed at any one amonga plurality of generally available access sites, the availability ofvascular access sites for the intravenous delivery of medicine for along period of time or for dialysis can be seriously diminished becausevascular access under such conditions has to be performed repeatedly.For example, hemodialysis typically requires from about 150 to about 200vascular access operations per year for a period that typically rangesform about 2 years to about 5 years.

It is therefore desirable to provide vascular access devices and systemsthat can be repeatedly accessed, and in particular repeatedly punctured,while avoiding the deleterious effects on the blood vessel itself. Thesesystems and devices should be biocompatible and in particular theyshould not significantly perturb the normal blood flow within the bloodvessel that is to be accessed. In addition, these systems and devicesshould be made of readily available materials that can be clinicallymanipulated according to known techniques. It is also desirable toprovide methods for repeatedly accessing blood vessels, and inparticular for repeatedly accessing veins in the practice ofvein-to-vein hemodialysis, so that vein accessibility is not diminishedby the repeated vein access.

The general object of this invention is to provide vascular accesssystems and devices that facilitate repeated vascular access whilereducing, or even eliminating, the deleterious effects that the vasculartissue would otherwise be subjected to. More specifically, it is anobject of this invention to provide vascular access systems and devicesthat permit access to the blood stream while avoiding repeated puncturesinto the blood vessel being accessed.

It is another object of this invention to provide vascular accesssystems and devices that can be attached to a blood vessel by knownanastomosis techniques.

It is another object of this invention to provide vascular accesssystems and devices that can be used for the intravenous long termdelivery of medicines and also be used in dialysis.

It is a further object of this invention to provide methods for externaltreatment of blood such as hemodialysis methods, and in particularvein-to-vein hemodialysis methods, that enable the practice ofhemodialysis between two blood vessels, such as two veins, whileavoiding deleterious effects on these vessels. These deleterious effectswould otherwise reduce blood vessel accessibility thus rendering thenumber of feasible hemodialysis operations unacceptably small.

These and other objects of this invention are preferably achieved bydevices that comprise an occlusal balloon in fluid communication with aport device, and by systems that comprise an occlusal balloon in fluidcommunication with a port device to be used in conjunction with a graftvessel that in turn is configured to be anastomosed to a blood vessel.

The devices and systems of this invention preferably feature materialsthat are suitable for their subcutaneous disposition. This featureadvantageously permits the placement of the vascular access systems anddevices at a location that is not directly exposed to externalpathogens.

The devices and systems of this invention preferably feature materialsthat can be repeatedly punctured and that are self-sealing. Thesefeatures advantageously permit multiple injection to and extraction fromthe vascular access systems and devices of a variety of fluids such asblood samples, biocompatible solutions, medicines, and blood to bedialyzed or to be received from a dialysis apparatus.

The devices and systems of this invention preferably incorporatefeatures that facilitate the exposure of the blood stream to desiredphysiologically effective (or bioactive) agents. This exposure isachieved by contact or by transport phenomena. In any case, thesefeatures advantageously permit, inter alia, the delivery into the bloodstream of medications at desired and controlled dosages. Anotheradvantage derived from these features is that the blood stream can beexposed to an agent that prevents the formation of blood clots.

The methods of this invention focus on repeated vascular access that isfacilitated by preferably subcutaneous devices and systems which can berepeatedly punctured while preserving their physical integrity,biocompatibility and operability. These characteristics advantageouslypermit the practice of hemodialysis according to the methods of thisinvention for the extended periods of time that are typically needed bypatients.

These and other objects, features, and advantages of the presentinvention will become more fully apparent from the following descriptionand appended claims, or may be learned by the practice of the inventionas set forth hereinafter.

BRIEF DESCRIPTION OF THE DRAWINGS

In order that the manner in which the above-recited and other advantagesand objects of the invention are obtained, a more particular descriptionof the invention briefly described above will be rendered by referenceto specific embodiments thereof which are illustrated in the appendeddrawings. Understanding that these drawings depict only typicalembodiments of the invention and are not therefore to be considered tobe limiting of its scope, the invention will be described and explainedwith additional specificity and detail through the use of theaccompanying drawings in which:

FIG. 1 is a partial cross sectional view of an embodiment of a vascularaccess system with an occlusal balloon.

FIG. 2 is a partial cross sectional view of another embodiment of avascular access system with a reinforced graft vessel that has anenlarged portion, and an occlusal balloon with a semipermeable membrane.

FIG. 3 is a partial cross sectional view of the port device of theembodiment shown in FIG. 2.

FIG. 4 shows a perspective view of an embodiment of a port device.

FIG. 5 is a partial cross sectional view of an embodiment of a vascularaccess system with two occlusal balloons, two semipermeable membranes,and a graft vessel with an enlarged portion.

FIGS. 6A-6D schematically illustrate different configurations of asemipermeable membrane at the delivery end of an occlusal balloon.

FIGS. 7A-7B schematically illustrate several steps in a technique toattach a semipermeable membrane to the delivery end of an occlusalballoon.

FIG. 8 schematically shows the practice of hemodialysis according to themethods of this invention.

FIG. 9 shows the time evolution of the osmotic pressure and the osmoticpressure and heparin transfer for a heparin aqueous solution with noalbumin.

FIG. 10 shows the time evolution of the osmotic pressure and the osmoticpressure and heparin transfer for a heparin aqueous solution with 1%albumin.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention relates to vascular access systems, devices andmethods, and in particular to venous access systems and devices, andmethods for external treatment of blood, particularly vein-to-veinhemodialysis, that permit access to the blood flow while avoidingrepeated punctures into the blood vessel being accessed. To this end, anexemplary embodiment of the system of the present invention includes thefollowing components: a graft vessel that is adapted for beinganastomosed to the blood vessel that is to be repeatedly accessed, anocclusal balloon, a port device, and a semipermeable membrane thatpermits the selective and controlled exposure of the blood flow to anagent such as a physiologically active agent.

Selective and controlled exposure to a physiologically active agent is,in some preferred embodiments, provided by letting such agent migratefrom the interior of an occlusal balloon into the blood in the vesselbeing accessed. This migration of a physiologically active agent ispreferably realized by diffusion across a semipermeable membrane ofadequately chosen porosity. In addition, preferred embodiments of thesemipermeable membrane function according to the present invention byletting the migration of an aqueous fluid from the blood stream in thevessel being accessed into the interior of an embodiment of an occlusalballoon. This migration of aqueous fluid is preferably realized bypermeation across a semipermeable membrane of adequately chosenporosity. By migrating from the blood stream into the interior of anembodiment of an occlusal balloon, this aqueous fluid keeps the occlusalballoon in a distended configuration by osmosis, thus preventing theinvasion of the anastomosed graft by blood from the accessed vessel.

FIG. 1 schematically and generally shows in a cross sectional viewrelevant features of this invention as illustrated by an exemplaryembodiment. Blood vessel 10 in this exemplary embodiment is accessedwith the aid of graft vessel 20 that is anastomosed to blood vessel 10at anastomosis site 21. Graft vessel 20 houses, in this particularembodiment, occlusal balloon 40 with a delivery end 42 and an access end44.

The anastomosed graft of this invention provides a passage forestablishing fluid communication with the lumen of the vessel, forexample a vein, being accessed. Methods, systems and devices foranastomosing a graft vessel to a blood vessel have been disclosed, forexample, in copending U.S. patent application Ser. No. 09/293,336, nowabandoned, which is entitled Methods, Systems and Apparatus forIntraluminally Directed Vascular Anastomosis, filed on Apr. 16, 1999,and U.S. application Ser. No. 09/293,617, now U.S. Pat. No. 6,248,117,which is entitled Anastomosis Apparatus for Use in IntraluminallyDirected Vascular Anastomosis, filed on Apr. 16, 1999. Bothapplications, including Ser. No. 09/293,336 and Ser. No. 09/293,617, areherein incorporated by reference in their entirety. The presentinvention, however, does not require a specific anastomosis techniquefor its implementation.

A plurality of factors may cause blood flowing in lumen 12 of bloodvessel 10 to coagulate in the region near anastomosis site 21 resultingin vessel thrombosis. These factors include the presence of foreignbodies used in the anastomosis procedure, irregularities at anastomosissite 21, and disrupted intima at anastomosis site 21. To prevent thisformation of blood clots, blood flowing in lumen 12 is exposed in theregion near to delivery end 42 to an anticoagulant agent that isprovided with the aid of occlusal balloon 40.

In addition to coagulation, blood flow stagnation in the region nearanastomosis site 21 should be minimized and preferably avoided. To thisend, occlusal balloon 40 is so configured as to be able to seal theanastomosis site in a way such that no significant cavity is formed atanastomosis site 21; the presence of a cavity or substantially recessedspace in this region would lead to blood flow stagnation or to a clot.In addition, a cavity or substantially recessed space can lead to theformation of unacceptably turbulent blood flow when the device isanastomosed to an artery.

Graft vessel 20 is shown in FIG. 1 as being anastomosed to blood vessel10 which is accessed at anastomosis site 21. Graft vessel 20 has portend 24 which is opposite to anastomosis end 22; port end 24 is in thisexemplary embodiment connected to port device 50. Graft vessel 20 andport device 50 are typically located subcutaneously and graft vessel 20is made of a material such as polytetrafluoroethylene (PTFE) or someother biocompatible self sealing material that can be punctured asschematically shown in FIG. 1 by hypodermic needle 58 or by any othermedical device that is ordinarily used to inject fluids in or to drawfluids from a cavity. As illustrated by the embodiment shown in FIG. 1,delivery end 42 of occlusal balloon 40 generally corresponds withanastomosis end 22 of graft vessel 20 in the sense that both ends aregenerally located in the region of the anastomosis site 21.

The exemplary embodiment of port device 50 shown in FIG. 1 comprisesconduit 52 that is connected in fluid communication at one of its endswith occlusal balloon 40 at access end 44. The opposite end of conduit52 can be externally accessed through a self-sealing aperture 54. Thisself-sealing aperture can be penetrated by a hypodermic needle or anyother medical instrument that is typically used to inject fluid into orto draw fluid from a cavity. Embodiments of the self-sealing apertureaccording to this invention are preferably made of silicone rubber. Portdevices such as port device 50 are common medical devices and hence nofurther detailed description of the structure of the connection of sucha port device to access end 44 is herein sketched. Commerciallyavailable port devices for vascular access include devices that aremarketed under the trademarks OmegaPort, TitanPort, and Vortex, byHorizon Medical Products, Manchester, Georgia, and under the trademarksP.A.S. Port and P.A.S. Port II by Smiths Industries Medical Systems, orSIMS Deltec, Inc., Saint Paul, Minn.

As shown in the example depicted in FIG. 1, port end 24 of graft vessel20 is detachably connected to port device 50 by a pressure device 51that exerts sufficient pressure to maintain the leak proof attachment ofgraft vessel 20 to port device 50. Pressure device 51 can in particularbe embodied by an O-ring or by any other device that exerts sufficientpressure to maintain the leak proof attachment of graft vessel 20 toport device 50. This leak proof attachment can be accomplished in otherembodiments of this invention by a threaded engagement, a snap jointengagement, a bound engagement, an adhesive bound engagement, or by anytype of leak proof engagement that is well known in the art. Embodimentsof the port device are preferably made of stainless steel or titanium,although other biocompatible materials can also be used, particularlyother biocompatible materials that are preferably resistant to theabrasion of sharp needle tips.

Occlusal balloon 40 can be inflated with fluid provided thereto throughport device 50, in which case occlusal balloon 40 prevents the flow ofblood into graft vessel 20 by occluding and effectively sealinganastomosis site 21. Occlusal balloon 40 can be selectively deflated bydrawing its fluid content through port device 50, in which case bloodflow from blood vessel 10 invades the interior of graft vessel 20through anastomosis site 21. Embodiments of inflatable balloonsaccording to the present invention, are made of any elasticbiocompatible material, such as rubber, PTFE, latex, and combinations ofthese materials. When the embodiment of the inflatable balloon comprisesa membrane that is attached to the balloon with an adhesive, the balloonmaterial is preferably gluable, such as silicone rubber.

When blood flow from blood vessel 10 reaches the interior of graftvessel 20 because occlusal balloon 40 is in a deflated configuration,graft vessel 20 can be punctured by a needle to perform, for example ahemodialysis. When the dialysis session is finished, occlusal balloon 40can be inflated again by injecting an appropriate fluid through portdevice 50 and any remaining blood left near access end 44 can be drawnout of this space and replaced with a fluid such as saline solution orany other appropriate biocompatible fluid.

In its inflated configuration, occlusal balloon 40 is filled with afluid that causes, or in some embodiments contributorily causes, theexpansion within elastic compliance limits of such balloon. In addition,delivery end 42 of occlusal balloon 40 is preferably manufactured toexpose the blood flow in blood vessel 10 near anastomosis site 21 to aphysiologically active agent such as an anticoagulant agent.

A preferred embodiment of this invention comprises an occlusal balloonwhich can be repeatedly inflated and deflated within its elasticcompliance limits. The occlusal balloon in its inflated configurationeffectively seals the graft vessel at the anastomosis site.

In some embodiments of this invention, the fluid injected into theocclusal balloon cannot diffuse out of the occlusal balloon, in whichcase it is this fluid that directly causes the inflation of the occlusalballoon. An occlusal balloon of this type is herein described as aself-contained occlusal balloon.

In other preferred embodiments of this invention, the occlusal balloonis configured with a semipermeable membrane that allows for fluidtransport out of and into the interior of the occlusal balloon, in whichcase the fluid injected into the occlusal balloon contributorily causesits initial inflation, with other phenomena, such as osmosis, causingthe occlusal balloon to remain in an inflated configuration.

The exposure of the blood in the vessel being accessed to aphysiologically active agent can be accomplished, in particular, bydelivering into the interior of occlusal balloon 40 a fluid thatcontains a physiologically active agent, particularly anticoagulantssuch as heparin at the appropriate dosage, and allowing this heparin tobe transported into luminal space 12 of blood vessel 10 across asemipermeable membrane of the adequate porosity that is part of deliveryend 42 of occlusal balloon 40. These features and elements of a vascularaccess device according to this invention function to provide aselective and controlled exposure, and more specifically, to provide aselective and controlled transport.

In this specific exemplary embodiment, this semipermeable membranepreferably allows the flow of aqueous fluid from the blood flow in bloodvessel 10 into the interior space of occlusal balloon 40 by osmoticpressure. Osmosis can be accomplished by delivering into the interior ofocclusal balloon 40 a fluid that contains a preferably biocompatiblesubstance that cannot permeate across the membrane through which heparinis delivered. An example of such substance is albumin. The fluid withinocclusal balloon 40 thus contributes in providing the adequateconditions for osmosis to take place and hence to the maintenance ofocclusal balloon 40 in an inflated configuration as heparin, or someother substance, diffuses from the interior of occlusal balloon 40 intothe blood flow in blood vessel 10.

In addition to, or instead of, heparin or another anticoagulant,occlusal balloon 40 of the present invention can be used to deliver amedication, and in particular a medication for a long term treatment ofa chronic disease. This medication can also be delivered by letting itdiffuse across a permeable membrane at delivery end 42 of occlusalballoon 40. In the exemplary embodiment shown in FIG. 1, heparin and anyother substance that diffuses through a semipermeable membrane atdelivery end 42 can be periodically supplied to the interior space ofocclusal balloon 40 by injection through port device 50.

In the practice of hemodialysis and also in the prolonged delivery ofmedicine for the treatment of a chronic disease, the occlusal balloon ofthis invention typically contains an aqueous solution that includes ahigh molecular weight substance that cannot diffuse through the pores ofthe chosen semipermeable membrane and at least one physiologicallyactive agent of a smaller molecular weight that can diffuse through thepores of the chosen semipermeable membrane. As indicated in thediscussion of the embodiment shown in FIG. 1, the preferred highmolecular weight substance is albumin and the preferred physiologicallyactive agent is typically heparin.

In some of the embodiments of this invention, heparin is thephysiologically active agent and also the solute whose concentrationgradient gives rise to the osmotic pressure that keeps the occlusalballoon inflated. The occlusal balloon holds in these embodiments arelatively large volume of solution so that the concentration of heparindoes not decrease too rapidly as a consequence of its diffusion rateacross the properly chosen semipermeable membrane.

The aqueous solution of albumin and heparin provides the concentrationgradient driving the osmotic process which in turn keeps the occlusalballoon in an inflated configuration. Osmosis in this context involvesthe diffusion of aqueous fluid from the blood in the blood vessel beingaccessed into the interior of the occlusal balloon through the pores ofan appropriately selected semipermeable membrane that is in contact withthe blood flow at the anastomosis site. Albumin used in this inventionis preferably human albumin with a molecular weight of approximately65000.

Heparin diffuses through the pores of such semipermeable membrane intothe blood in the blood vessel which is being accessed, thus preventingthe coagulation of blood that might otherwise take place as aconsequence of a variety of factors that are associated with thefeatures of the anastomosed structures. The molecular weight of theheparin preferably used in embodiments of the present invention rangesfrom about 500 to about 18000. Heparin inhibits reactions that lead tothe clotting of blood and the formation of fibrin clots both in vitroand in vivo. The clinical pharmacology of heparin is that of a substancethat acts at multiple sites in the normal coagulation system. Inparticular, small amounts of heparin in combination with antithrombinIII (heparin cofactor) can inhibit thrombosis by inactivating activatedFactor X and inhibiting the conversion of prothrombin to thrombin. Onceactive thrombosis has developed, larger amounts of heparin can inhibitfurther coagulation by inactivating thrombin and preventing theconversion of fibrinogen to fibrin. It is reported that heparin alsoprevents the formation of a stable fibrin clot by inhibiting theactivation of the fibrin stabilizing factor.

In choosing the appropriate concentrations of albumin and heparin,however, a variety of determining factors have to be taken intoconsideration. Heparin and albumin associate to some extent. Thisassociation leads to the effective sequestering of heparin that is notavailable to diffuse into the blood stream. In addition, some of thealbumin can be adsorbed on the semipermeable membrane, thus decreasingthe effective concentration of albumin that influences osmosis.

The concentration of albumin is accordingly determined so that theosmotic pressure is comparable to and slightly greater than the vascularpressure in the blood vessel being accessed. For example, venouspressure is typically in the approximate range of about 5 mmHg to about15 mmHg, and rarely exceeds 30 mmHg, in which case a venous vascularaccess according to this invention should preferably provide an albuminsolution in the occlusal balloon at an osmotic pressure slightly greaterthan 30 mmHg, such as in the approximate range of about 35 mmHg to about45 mmHg.

“Nominal molecular weight pore size membrane” in this contextcharacterizes a semipermeable membrane whose pore size is such thatparticles whose molecular weight is less than the given nominalmolecular weight are able to diffuse through the membrane's pores,whereas substances whose molecular weight is greater than or about equalto the given nominal molecular weight cannot diffuse through themembrane's pores. Unless otherwise indicated, molecular weights givenherein are expressed in Daltons; albumin concentration units givenherein are expressed as a percentage that refers to mass in grams ofalbumin in 100 ml of solution, and heparin concentration units areexpressed as International Units (IU) heparin per ml of solution.

The preferred membrane used in embodiments of this invention is formedfrom polyethersulfone and is most preferably the semipermeable materialsold as Biomax from Millipore. This semipermeable membrane is availablein several nominal molecular weight pore sizes in the range from about5000 to about 50000. Preferred membranes for embodiments of thisinvention are characterized by a pore size in the range from about 30000to about 50000 nominal molecular weight. Among these types ofsemipermeable membrane, a more preferred type is a membrane with anominal molecular weight pore size of about 50000.

In general, preferred membranes for embodiments of this invention areultrafiltration membrane materials. In addition to the Biomax membrane,Millipore provides other membranes such as regenerated cellulosemembranes sold as Amicon 4M which has a nominal molecular weight poresize of about 1000 to about 100000, and hydrophilic polysulfone membranesold as Amicon Zm which has a nominal molecular weight pore size ofabout 500 to about 500000.

Generally, semipermeable membrane base materials include polymericmaterials such as polytetrafluoroethylene, polysulfone, polyamide,polyacrylonitrile, and cuprophane of the adequate pore size, althoughthe hydrophobicity of some polymers requires the treatment of the basematerial prior to its use as a semipermeable membrane.

Clinical dialyzer materials that can be used in the context of thisinvention include a cuprophane material sold as CF 15.11 from BaxterHealth Care Corp., Deerfield, Ill.; cellulose acetate material sold asCOAK 4000 and saponified cellulose ester sold as SCE from Cordis DowMedical, Miami Lalles, Fla.; polymethylmethacrylate Filtryzer membranefrom Toray, Tokyo, Japan; cuprammonium material sold as Rayon fromTerumo, Japan; and cuprophane material sold as Hemoflow D3 andpolysulfone material sold as Hemoflow 60 from Fresenius A. G., Germany.

Semipermeable membranes used in different embodiments of this inventioncan be attached to the delivery end of the occlusal balloon with orwithout a backing that provides structural support, depending on thetype of membrane being used. Also, the occlusal balloon material at thedelivery end can in some embodiments provide structural support to thesemipermeable membrane.

The polyethersulfone membrane used in embodiments of this invention arepreferably conditioned prior to its use by immersing it in an albuminsolution. For example, by immersing it in a 10% albumin aqueous solutionfor about one week. Once conditioned, the membrane can be repeatedlyused as long as it is not allowed to substantially dehydrate.

FIG. 2 shows another exemplary embodiment of the present invention inwhich an occlusal balloon is used for sealing the end of the graftvessel at the anastomosis site. Blood vessel 110 is being accessed withthe aid of graft vessel 120 that is shown as being anastomosed to bloodvessel 110 at anastomosis site 121. Graft vessel 120 houses, in thisparticular embodiment, occlusal balloon 140 with a delivery end 142 andan access end 144.

To prevent the formation of blood clots, blood flowing in lumen 112 isexposed in the region near to delivery end 142 to an anticoagulant agentthat is provided with the aid of occlusal balloon 140. Instead of, or inaddition to, an anticoagulant agent, blood flowing in lumen 112 can beexposed to other substances. In this particular embodiment, thesubstances to which blood is exposed are initially contained in theinterior of occlusal balloon 140 and they are delivered into the bloodstream at delivery end 142 which is so configured as to allow diffusiontransport into the blood stream of substances, and in particulardiffusion of an anticoagulant agent.

Delivery end 142 is specifically configured in the embodiment of thisinvention shown in FIG. 2 with the occlusal balloon material at deliveryend 142 being perforated and adjacent to a suitable semipermeablemembrane 143. In this configuration, a substance that is to be deliveredinto the blood stream can pass through the perforations at delivery end142, reach semipermeable membrane 143, and diffuse into the blood streamthrough the pores of semipermeable membrane 143. Instead ofperforations, occlusal balloon material can have at delivery end 142 anyother feature that performs the same function that is performed byperforations, namely allowing for the passage of fluid from and towardssemipermeable membrane 143.

In addition to coagulation, blood flow stagnation in the region nearanastomosis site 121 must be minimized and it is preferably avoided. Tothis end, occlusal balloon 140 is so configured as to be able to sealthe anastomosis site in a way such that no significant cavity is formedat anastomosis site 121. As indicated regarding the embodiment shown inFIG. 1, the presence of a cavity or substantially recessed space in thisregion may lead to blood flow stagnation, clot formation, and, inarteries, formation of unacceptably turbulent blood flow.

Graft vessel 120 is shown in FIG. 2 as being anastomosed to blood vessel110 which is accessed at anastomosis site 121. Graft vessel 120 has portend 124 which is opposite to anastomosis end 122; port end 124 is inthis exemplary embodiment connected to port device 150. Graft vessel 120and port device 150 are typically located subcutaneously and graftvessel 120 is made of a material such as polytetrafluoroethylene (PTFE)or some other biocompatible self sealing material that can be puncturedas schematically shown in FIG. 2 by hypodermic needle 158 or by anyother medical device that is ordinarily used to inject fluids in or todraw fluids from a cavity.

Graft vessel 120 as shown in the embodiment depicted in FIG. 2 ispreferably provided with an enlarged portion 125 near anastomosis end122. This enlarged portion provides a recessed space into which deliveryend 142 and semipermeable membrane 143 collapse when occlusal balloon140 is deflated.

The exemplary embodiment of port device 150 shown in FIG. 2 comprisesconduit 152 that is connected in fluid communication at one of its ends,access end 144, with occlusal balloon 140. The opposite end of conduit152 can be externally accessed through a self-sealing aperture 154. Thisself-sealing aperture can be penetrated by a hypodermic needle or anyother medical instrument that is typically used to inject fluid into orto draw fluid from a cavity. As indicated regarding the embodiment shownin FIG. 1, port devices such as port device 150 are common medicaldevices and hence no detailed structure of the connection of such portdevice to access end 144 is herein sketched.

As shown in the example depicted in FIG. 2, port end 124 of graft vessel120 is detachably connected to port device 150 by a pressure device 151.As indicated in the discussion of the embodiment depicted in FIG. 1,pressure device 151 can be embodied by any device that exerts sufficientpressure to maintain the leak proof attachment of graft vessel 120 toport device 150. This leak proof attachment can be accomplished in otherembodiments of this invention by other engagements as disclosed in thepreceding discussion of the embodiment shown in FIG. 1.

The graft vessel of this invention can be provided with a reinforcementstructure in its entire length or in part of its length. An exemplaryembodiment of such reinforcement structure is schematically shown in theembodiment depicted in FIG. 2 by reinforcement rings 123. These ringsare preferably embedded into the material, for example PTFE, of whichgraft vessel 120 is made, but they can also be partially embedded orexternally disposed on graft vessel 120 and attached thereto. Instead ofrings, these reinforcement structures can be embodied by a helical coil,longitudinal features aligned with the longitudinal axis of occlusalballoon 140, longitudinal features that present any one amongst avariety of possible chiral configurations, crisscross stripes, or anyother reinforcement pattern that is known to provide structuralreinforcement to a flexible, generally cylindrical body. Embodiments ofthese reinforcement structures are preferably made of plastic.Reinforced PTFE graft material that can be used as graft vessel 120 issold under the name IMPRA by Bard, under the name MEDOX from BostonScientific and by W. L. Gore, of Phoenix, Ariz.

Typical embodiments of this invention are configured to be adapted to ananastomosis fenestra of about 4 mm, in which case the internal diameterof the graft vessel is about 6 mm. Embodiments of the graft vessel thatare provided with an enlarged portion such as enlarged portion 125 inFIG. 2 are configured so that the internal diameter of the graftvessel's enlarged portion is between about 8 mm and about 9 mm. Atypical length of embodiments of the occlusal balloon from its deliveryend to this access end is preferably about 2 cm. The length of the graftvessel is preferably chosen so that it provides a plurality of puncturesites.

Operations such as inflation, deflation, and use of the embodimentschematically depicted in FIG. 2 are generally performed as describedwith regard to the embodiment shown in FIG. 1.

Embodiments of this invention that are provided with an occlusal balloonare preferably configured in a way such that the access end of theocclusal balloon and the port device are separated by severalcentimeters. In some embodiments, however, the inflated occlusal ballooncan extend up to and be in contact with the port device.

FIG. 3 schematically shows a cross-sectional view along plane 5-5′ inFIG. 2 of an embodiment of the port device therein depicted. Elements inthe cross sectional view are labelled with the same numbers as thecorresponding elements are labelled in FIG. 2.

FIG. 4 shows an exploded perspective view of another embodiment of aport device comprising a body 186, a self sealing plug 182 and means forkeeping self sealing plug 182 within body 186 effectively sealing cavity184. In some embodiments of this invention, self sealing plug 182 isembodied by a sheet of silicone. This means for keeping self sealingplug 182 is embodied in the example shown in FIG. 4 by compression ring180. Body 186 is provided with connector 188 to establish leak prooffluid communication between cavity 184 and the interior of an occlusalballoon. A passage, such as passage 190, is configured for effectivelyestablishing fluid communication between cavity 184 and the interior ofan occlusal balloon attached to connector 188. This connector is in someembodiments provided with features such as flanges or ridge 192 forassisting in establishing leak proof communication with an occlusalballoon.

Some embodiments of this invention may be provided with more than oneocclusal balloon. FIG. 5 shows another exemplary embodiment of thepresent invention which is provided with two occlusal balloons 340 and341.

Blood vessel 310 is being accessed with the aid of graft vessel 320 thatis shown in FIG. 5 as being anastomosed to blood vessel 310 atanastomosis site 321. Graft vessel 320 houses in this particularembodiment first occlusal balloon 340 with first delivery end 345 andfirst access end 344, and second occlusal balloon 341 with seconddelivery end 343 and second access end 346.

Blood flowing in lumen 312 is exposed in the region near to deliveryends 343 and 345 to agents that are provided with the aid of occlusalballoons 340 and 341. When more than one agent is to be provided, therange of molecular weights of such agents may be so broad that a singlemembrane might not be adequate for the diffusion of the different agentsinto the blood stream. Even if a single membrane were adequate,conditions to be satisfied regarding the replacement, mixing andcompatibility of the agents might require that they be kept in differentocclusal balloons. In the arrangement shown in FIG. 5, for example,occlusal balloon 340 may contain an aqueous solution of albumin andheparin. Heparin would be delivered into the blood stream by diffusionacross a semipermeable membrane at delivery end 345 and the balloonwould be kept inflated by osmotic pressure due to the diffusion of anaqueous fluid across the same membrane into the interior of occlusalballoon 340. Occlusal balloon 341 could contain a solution of one ormore physiologically active agents, such as medications, that would bedelivered into the blood stream by diffusion across a semipermeablemembrane at delivery end 343.

The embodiment shown in FIG. 5 and equivalents thereof are preferredembodiments for long term peripheral vascular access, particularly forvenous access for parenteral medication. Membrane 343 in theseembodiments is suitable for allowing slow diffusion of small molecularweight solutes, such as medication that requires parenteraladministration, including antibiotics, small peptides, and hormones.

Delivery ends 343 and 345 of occlusal balloons 340 and 341 are soconfigured as to be able to seal the anastomosis site in a way such thatno significant cavity is formed at anastomosis site 321. As indicatedregarding the embodiment shown in FIGS. 1 and 2, the presence of acavity or substantially recessed space in this region would lead toblood flow stagnation or to the formation of unacceptably turbulentblood flow, both of which would be expected to predispose to thrombosis.

Graft vessel 320 is shown in FIG. 5 as being anastomosed to blood vessel310 which is accessed at anastomosis site 321. Graft vessel 320 has portend 324 which is opposite to anastomosis end 322; port end 324 is inthis exemplary embodiment is connected to port device 350. Graft vessel320 and port device 350 are typically located subcutaneously and graftvessel 320 is made of a material such as polytetrafluoroethylene (PTFE)or some other biocompatible self sealing material that can be puncturedas schematically shown in FIG. 5 by hypodermic needle 358 or by anyother medical device that is ordinarily used to inject fluids in or todraw fluids from a cavity.

As indicated in the discussion regarding the exemplary embodiment shownin FIG. 2, graft vessel 320 may have an enlarged portion nearanastomosis end 322 like enlarged portion 125 shown in the embodimentdepicted in FIG. 2. Such an enlarged portion provides a recessed spacefor accommodating collapsing delivery ends 343 and 345 as occlusalballoon 340 is deflated. Deflation of occlusal balloon 340 isaccompanied when necessary by deflation of occlusal balloon 341.

The exemplary embodiment of port device 350 shown in FIG. 5 comprisesconduits 352 and 353. One of the ends of conduit 352 is in fluidcommunication with occlusal balloon 340 and the opposite end can beexternally accessed through self-sealing aperture 354. Analogously, oneof the ends of conduit 353 is in fluid communication with occlusalballoon 341 and the opposite end can be externally accessed throughself-sealing aperture 355. Self-sealing apertures 354 and 355 can bepenetrated by a hypodermic needle or any other medical instrument thatis typically used to inject fluid into or to draw fluid from a cavity.Self-sealing apertures 354 and 355 may be arranged relative to eachother in port device 350 in a variety of ways. For example, they can belocated next to each other and aligned on the same side of port device350 as shown in FIG. 5, or they can be located at any desired anglerelative to each other and facing along different axial directions. Asindicated regarding the embodiments shown in FIGS. 1 and 2, port devicessuch as port device 350 are common medical devices and hence no detailedstructure of the connection of such port device to access ends 344 and346 is herein sketched.

It is understood that configurations of balloons 340 and 341 that departfrom that shown in FIG. 5 while including the basic elements thereinshown are within the scope of this invention. For example, access ends344 and 346 can in some embodiments be flush with respect to each other,or balloon 341 can in some embodiments be contained within balloon 340.In other embodiments, balloons 340 and 341 are placed within the graftvessel essentially next to each other, in which case the balloon that islocated closer to the port device preferably has an elongated deliveryend that extends substantially up to the anastomosis site. Either one ofaccess ends 344 or 346, or both access ends, can in some embodimentsextend back to port device 350 and be in contact engagement with suchport device, particularly in the inflated configuration. In still otherembodiments, balloon 341 can be predominantly located in the spacebetween access end 344 and port device 350, a configuration that wouldbe preferred if balloon 341 had to be subject to, for example, specialpressure conditions. In this latter case, an additional conduit, notshown in FIG. 4, would establish fluid communication between thedelivery end of balloon 341 and membrane 343. Whether including only oneocclusal balloon or a plurality of balloons, the foregoing featuresdescribe a variety of embodiments of this invention. In addition, theaccess end of one or the access ends of several balloons of someembodiments of this invention can be directly connected to port device350 either in the form of an integral attachment, a detachableconnection, or by bonding, such as by adhesive bonding. Theseembodiments are particularly suitable when any portion of the conduitconnecting an access end of a balloon with a self-sealing aperture inthe port device has to be eliminated.

Port devices according to this invention can also be embodied by portdevices that have additional ports for conventional uses, such as portsthat are configured to operate probes, sampling devices, imaging devicesand imaging device elements, or medical intervention assisting devices.

As shown in the example depicted in FIG. 5, port end 324 of graft vessel320 is detachably connected to port device 350 by a pressure device 351that exerts sufficient pressure to maintain the attachment of graftvessel 320 to port device 350 leak proof. The pressure device 351 ispreferably an embodied by an O-ring. As noted in the description of theembodiments shown in FIGS. 1 and 2, this leak proof attachment can beembodied by threaded engagement, a snap joint engagement, a boundengagement, in particular an adhesive bound engagement, or by any typeof leak proof engagement that is well known in the art.

The semipermeable membrane in embodiments of this invention that allowfor diffusion of matter into the blood stream can be attached to anocclusal balloon in a variety of configurations. Three examples of suchconfigurations are shown in FIGS. 6A-6C. FIG. 6A depicts a configurationlike that of the embodiment shown in FIG. 1, where occlusal balloonmaterial at the delivery end 401 a is punctured, perforated, or itsstructure is such that it allows for the passage of fluid across it sothat it is the semipermeable membrane 402 a that determines whichspecies diffuse across it into and from the blood stream. In a preferredconfiguration shown in FIG. 6B, occlusal balloon material at deliveryend 401 b is provided with a window that generally corresponds with afunctional portion of semipermeable membrane 402 b. In anotherconfiguration shown in FIG. 6C, occlusal balloon material at deliveryend 401 c is provided with features 409 that brace the edges ofsemipermeable membrane 402 c.

The interior of the occlusal balloon of this invention is in fluidcommunication with the self-sealing aperture in the port device throughan essentially leak-proof connection. This connection is achieved in anyof the forms known in the art. Consequently, the detailed features shownin the accompanying Figures pertaining to this connection are merelyexemplary and they are not to be regarded as descriptive of a unique wayof achieving such connection.

Some embodiments of this invention are provided with a graft vessel thathas enlarged portion 125 for housing the collapsed balloon as shown bythe phantom lines in FIG. 2. This configuration, or any other equivalentconfiguration, reduces any possible impediment to the blood flow throughthe graft vessel that could otherwise be caused by the deflated balloon.Although enlarged portion 125 is not shown for the sake of clarity inthe illustrations of the embodiments shown in FIGS. 1 and 5, these andany other embodiment of this invention, can optionally be provided withsuch enlarged portion of the graft vessel.

FIG. 6D schematically shows a portion of an embodiment of an occlusalballoon in which semipermeable membrane 402 d is integrally formed inocclusal balloon material at delivery end 401 d. In one embodiment ofthis invention, the occlusal balloon is made of, for example, PTFE thatis impermeable to the solvent and solute or solutes in the occlusalballoon, and the delivery end of the balloon is made of porous PTFE thatembodies semipermeable membrane 402 d.

In addition to single layer and bi-layer configurations described abovefor the disposition of the semipermeable membrane at the delivery end ofthe occlusal balloon, other configurations are also possible. Theseadditional configurations include a tri-layer configuration andconfigurations in which the semipermeable membrane is sandwiched betweentwo layers of material, one at each side of the membrane, that allow forthe passage of fluid from and to the membrane.

Preferably, the shape of the functional portion of the semipermeablemembrane used in some embodiments of this invention is generallycircular, in which case corresponding features at the delivery end ofthe occlusal balloon are also generally circular. These shapes, however,are not unique or determinative of the characteristics and functions ofthe vascular access device of this invention, and other geometricalshapes can also be used, particularly when the base materials ormanufacturing tools can more efficiently be used with noncircularmembranes.

The occlusal balloon of specific embodiments of this invention at itsdelivery end and the membrane or membranes therein located present agenerally curved surface that slightly protrudes out of the occlusalballoon's body. This generally curved surface is preferably convex onthe side exposed to the blood stream of the blood vessel being accessed.This preferred shape is consistent with the slightly greater pressurewithin the occlusal balloon relative to the vascular pressure in theblood vessel being accessed by an embodiment of a device according tothis invention.

Although a variety of techniques can be relied on to attach asemipermeable membrane to the delivery end of an occlusal balloon asshown in FIG. 6B, a preferred technique comprises the steps of placing aprotective material 510 between occlusal balloon delivery end 512 andsemipermeable membrane and bonding, preferably with a biocompatibleadhesive, contour 512 of semipermeable membrane to the terminal end ofthe occlusal balloon as schematically shown in FIG. 7A. Occlusal balloonmaterial 518, which may be formed from expandable material such assilicone or latex, is subsequently cut as indicated by broken arrowsA-A′, thus obtaining the type of configuration shown in FIG. 7B, wherefunctional region 520 of the semipermeable membrane is typicallysurrounded by small non-functional portions 522 bound to the occlusalballoon material.

Although preferred embodiments of occlusal balloons according to thisinvention include a semipermeable membrane that allows for transport andis part of the osmosis that keeps the occlusal balloon inflated, otherembodiments of the occlusal balloon do not include any semipermeablemembrane. For example, some embodiments of the occlusal balloon areinflated by the injection of a fluid that is kept within the balloonwhile it is inflated, with no osmosis contributing to its distension.These embodiments are configured so that the exposure to aphysiologically active agent of the blood in the vessel being accessedis accomplished by merely subjecting the blood stream to contact withthe agent rather than by relying on diffusion across a membrane andsubsequent diffusion in the blood stream. The effects of this contactare predominantly in situ or local effects. These type of occlusalballoons are self-contained occlusal balloons.

When the physiologically active agent is heparin, in situ prevention ofclot formation is preferably achieved by subjecting the blood stream tocontact with heparin in a heparin immobilizing biocompatible material atthe delivery end of the self-contained occlusal balloon. Heparinimmobilizing materials include polyvinyl alcohol; surface-modifiedpolymeric biomaterials with poly(ethylene oxide), albumin, and heparin;derivatized dextrins; polymers with hydrophilic spacers;vinyl-pyridine-grafted styrene-butadiene-styrene triblock copolymer; anddimethyl-amino-ethyl-methacrylate-grafted styrene-butadiene-styrenetriblock copolymer.

Furthermore, a multifunctional thrombo-resistant coating can beincorporated on the delivery end of an occlusal balloon. This coatingincludes a siloxane surface onto which a plurality of amine functionalgroups have been bonded. Covalently bonded to the amine functionalgroups are a plurality of poly(ethylene oxide) chains, such that asingle poly(elthylene oxide) chain is bonded to a single aminefunctional group. A plurality of different bioactive molecules, designedto counteract specific blood-material incompatibility reactions, arecovalently bonded to poly(ethylene oxide) chains, such that a singlebioactive molecule is coupled to a single poly(ethylene oxide) chain.Methods of manufacturing these materials have been previously described.See, for example, International Patent Applications Nos. PCT/US89/01853and PCT/US91/02415, which are herein incorporated by reference in theirentirety. The resulting siloxane that is so manufactured contains aplurality of different bioactive molecules capable of reacting withblood components which come in proximity to the siloxane surface inorder to resist blood-material incompatibility reactions.

In the preferred embodiments of the occlusal balloon of this inventionwith a semipermeable membrane, the physiologically active agent iseffective at the release site, namely in situ. The dosage can beregulated so that the active agent is effective systemically because theactive agent circulates with the blood stream. This type of sources ofphysiologically active agents are herein described as permeating sourcesof physiologically active agents, and they include embodiments such asthose shown in FIGS. 6A-6D. The dose required to achieve theanticoagulant effect locally is much less than a systemicallytherapeutic dose, thus the long term risk associated with in situeffects is less than the risk associated with full systemicanticoagulation.

When the physiologically active agent is provided by immobilizing it ona self-contained occlusal balloon, the active agent is predominantlyeffective in situ, at or near the contact site. Such sources ofphysiologically active agents are herein described as in-situ sources ofphysiologically active agents. They include embodiments of the deliveryend of an occlusal balloon on which the physiologically active agent isattached at the outer surface that is exposed to the blood flow.

In addition, other embodiments of this invention incorporate aself-contained balloon that provides a source of at least onephysiologically active agent whose effects are manifested in situ andsystemically without transport across a semipermeable membrane. In theseembodiments, the physiologically active agent is typically released by asubstance that is incorporated on the delivery end of the occlusalballoon that is exposed to the blood flow. This type of sources ofphysiologically active agents are herein described as nonpermeatingsources of physiologically active agents. For example, when thephysiologically active agent is an anticoagulant, nitrogen oxidereleasing polymers can be incorporated on the delivery end of theocclusal balloon so that NO is released into the blood stream. Examplesof NO-releasing polymers include diazeniumdiolates added to plasticssuch as polyvinylchloride and polyurethane. In this case,diazeniumdiolates include specific compounds such as sodium1-(N,N-diethylamino)diazen-1-ium-1,2-diolate, disodium1-[2(S)-carboxylatopyrrolidin-1-yl]diazen-1-ium-1,2-diolate, sodium1-(piperazin-1-yl)diazen-1-ium-1,2-diolate, and1-{N-methyl-N-[6-(N-methylammonio)hexyl]amino}diazen-1-ium-1,2-diolate.

The features of each one of the herein described embodiments of theocclusal balloon are not meant to be exclusive of features of otherembodiments that can be incorporated in the same occlusal balloon torender a functional combination. For example, an occlusal balloon with asemipermeable membrane can also incorporate a source of aphysiologically active agent for predominantly in-situ effects, and/orincorporate a source of a physiologically active agent for in situ andsystemic effects of the type described in relation to embodiments ofself-contained occlusal balloons.

A vascular access with a system according to this invention ispreferably created by first performing a vascular anastomosis to attacha graft vessel to the blood vessel that is being accessed, and thenplacing an occlusal balloon within the graft vessel. This occlusalballoon may be provided with a port device already attached to it, orthe port device may be subsequently attached to the occlusal balloon byconventional techniques. Once a vascular access system according to thisinvention is placed at the access site, the entire system preferablyremains subcutaneously placed for its use in procedures such asdialysis, in particular hemodialysis, and drug delivery.

It is understood that elements of any embodiment of the vascular accesssystem according to this invention may be provided with suitableradio-opaque markings so that its location or particular configurationcan be externally observed. This markings can be particularly usefulwhen incorporated in the vascular graft or in the occlusal balloon.

FIG. 8 schematically illustrates an embodiment of a method forexternally treating blood according to this invention. In the exampleshown in FIG. 8, blood is extracted through an extraction vascularaccess apparatus such as the embodiment of extraction vascular accessapparatus 5, and delivered through a delivery vascular access apparatussuch as the embodiment of delivery vascular access apparatus 5′. Becausethe vascular access apparatus of this invention permits multiplevascular access, whether any given vascular access apparatus is employedin any specific treatment episode as an extraction or a deliveryapparatus is a matter of convenience and choice. In addition, once bloodhas been extracted through an extraction vascular access apparatus andthere is an available delivery vascular access apparatus to return theblood flow to a blood vessel, such extracted blood can be subjected to ahemodialysis or to any other blood treatment. Consequently, the term“hemodialysis” in the context of this invention is understood to broadlyrefer to external treatment of blood, including an actual hemodialysistreatment, and any other treatment of blood that is performed outside apatient's body, and which requires the extraction, treatment andsubsequent delivery of the treated blood to the patient.

Blood vessels 90 and 90′ represent the blood vessels involved in thetreatment process. When blood is extracted from blood vessel 90, it issubjected to treatment, and it is subsequently returned to blood vessel90′, blood vessel 90 is referred to as the extraction blood vessel andblood vessel 90′ is referred to as the delivery blood vessel. Althoughthe apparatus, systems and methods of this invention are suitable forthe practice of a variety of external treatments of blood, they areparticularly suitable for the practice of vein-to-vein hemodialysis. Inthis case, blood vessels 90 and 90′ would represent the vein from whichblood is extracted and the vein to which dialyzed blood is injected,respectively.

An embodiment of an apparatus or system according to this invention isattached to each one of blood vessels 90 and 90′ as schematically shownin FIG. 8 by embodiments and 5′, respectively. These embodiments areanastomosed at sites 65 and 65′, and they can be embodiments of any ofthe foregoing vascular access devices and systems of this invention andcombinations thereof. For the practice of a preferred method accordingto this invention, these embodiments comprise occlusal balloons 60 and60′, port devices 30 and 30′, and conduits 63 and 63′.

In some embodiments of this invention, port devices 30 and 30′, togetherwith occlusal balloons 60 and 60′, define respective chambers 15 and15′. Occlusal balloons 60 and 60′ are preferably disposed within graftvessels 66 and 66′ in these embodiments so that chambers 15 and 15′allow for the injection therein of a biocompatible fluid, such asisotonic saline solution. In other embodiments of this invention, nosignificant chamber or significant volume is left between occlusalballoons 60 and 60′ and respective port devices 30 and 30′. The volumeoccupied by distended occlusal balloon 60, plus optionally the volume ofchamber 15, defines an occludable interior in vascular access apparatus5 that is configured for receiving a fluid such as blood. Similarly, thevolume occupied by distended occlusal balloon 60′, plus optionally thevolume of chamber 15 ′, defines an occludable interior in vascularaccess apparatus 5′ that is configured for receiving a fluid such asblood.

As indicated in the description of preferred embodiments of thisinvention, graft vessels 66 and 66′ and port devices 30 and 30′ areself-sealing, so they can be repeatedly accessed without requiringreplacement or additional sealing procedures after each treatmentepisode. Access is preferably performed by appropriately puncturing thegraft vessels and port devices as desired. The interior of the occlusalballoon is preferably accessed through the corresponding port device,while the interior of the graft vessel is preferably accessed bydirectly puncturing the graft vessel wall.

Occlusal balloons that selectively and controllably expose the bloodflow in vessels 90 and 90′ to a physiologically active agent arepreferred for the practice of the methods of this invention. This can beachieved by any of the occlusal balloon embodiments to this effect thathave been described hereinabove and their equivalent devices. Vascularaccess apparatus 5 and 5′ preferably remain subcutaneously placed duringthe practice of hemodialysis and also during the intervening periodsbetween hemodialysis episodes.

Hemodialysis, or any other external blood treatment, is preferablyperformed according to methods of this invention by extracting bloodfrom blood vessel 90 through vascular access apparatus 5, having thisextracted blood dialyzed, and returning it by injecting it into bloodvessel 90′ through vascular access apparatus 5′. Extraction of blood ispreferably performed with occlusal balloon 60 in a deflatedconfiguration. Similarly, injection of blood is preferably performedwith occlusal balloon 60′ in a deflated configuration. Because the wallsof graft vessels 66 and 66′ are repeatedly punctured in repeatedhemodialysis episodes, blood vessels 90 and 90′ remain viable andunaffected by the repeated access. This procedure facilitatesvein-to-vein hemodialysis because the number of venous sites that areavailable for extended periods of time for the practice of hemodialysisis very limited. Furthermore, the practice of vein-to-vein hemodialysisis a desirable dialysis practice because AV (arterio-venous) grafthemodialysis typically leads to venous hyperplasia and stenosis.

Blood flow into the interior of vascular access apparatus 5 or 5′ isachieved by deflating occlusal balloon 60 or 60′, respectively. This canbe achieved by drawing the fluid that keeps occlusal balloon 60 in adistended configuration through port device 30, which is maintained influid communication with occlusal balloon 60 through conduit 63. Ananalogous operation can be performed to achieve blood flow into theinterior of vascular access apparatus 5′, which involves the deflationof balloon 60′ by drawing fluid through conduit 63′ and port device 30′.When blood flow into graft vessels 66 and 66′ has been allowed,hemodialysis or any other external blood treatment can proceed in aconventional manner. For this purpose, graft vessels 66 and 66′ arepunctured and blood is allowed to flow from vessel 66 to vessel 66′.When necessary, blood flow is forced with an appropriate pump.

Depending on the specific treatment to which the blood is subjectedexternally, the device that provides such treatment is part of the fluidcommunication between the extraction vascular access apparatus and thedelivery vascular access apparatus. In certain treatments, such asirradiation, the blood flow is exposed to the treating effects withoutactually being in fluid communication with the device that provides sucheffects. Since the blood flow must interact in some external manner withthe device that provides the treatment, it is said that the fluidcommunication between the extraction vascular access apparatus and thedelivery vascular access apparatus encompasses communication with ablood treating device.

Examples of external blood treatments that can be performed with thepresent invention include plasmapheresis, cytopheresis, hemodialysis,apheresis, hemoperfusion, and hemofiltration.

In some of these treatments, such as plasmapheresis—also known as plasmaseparation or plasma exchange—, whole blood is removed from the body,the bloods cellular components are separated in a blood treatmentdevice, and subsequently reinfused in a saline solution or some otherplasma substitute, thus depleting the body's own plasma withoutdepleting its blood cells. In this case, the external treatment of bloodis typically performed with a cell separator. Plasmapheresis iscurrently widely accepted for the treatment of myasthenia gravis,Lambert-Eaton syndrome, Guillain-Barré syndrome, and chronicdemyelinating polyneuropathy. An average course of plasma exchanges issix to ten treatments over two to ten weeks, with some centersperforming one plasmapheresis session per week and other centersperforming more than one session per week. Patients undergoingplasmapheresis are typically administered blood anticoagulantmedications, and the blood treatment device includes a plasmapheresisseparator. Plasmapheresis and cytopheresis are specific instances of themore general apheresis, which is the withdrawal of whole blood from thebody, separation of one or more components, and return by transfusion ofthe remaining blood to the donor.

Hemoperfusion is the technique of passing blood extracted from the bodythrough an extracorporeal sorbent column for the purpose of removingharmful substances. In one practice of hemoperfusion, blood is passedthrough a blood treatment device that comprises a biocompatiblehemoperfusion cartridge that contains activated carbon adsorbent coatedwith an antithrombogenic heparin-hydrogel. This technique permits theremoval of a variety of toxins in the blood, and it is used in thetreatment of drug overdoses, hepatic failure, encephalopathy, andremoval of chelated aluminum from hemodialysis patients.

Hemodialysis is one of the more common forms of dialysis used in theUnited States. In hemodialysis, a hemodialyzer, or artificial kidney,takes the place of failed kidneys which may have lost up to 80 or even90% of their functions. Patients with chronic kidney or renal failureneed dialysis to remove excess urea, fluid, electrolytes, minerals, andother wastes form the blood stream since the kidneys cannot perform thiscleansing. In this case, the external treatment of blood is typicallyperformed with a hemodialyzer as a blood treatment device. Anultrafiltration hemodialyzer is a hemodialyzer that uses fluid pressuredifferentials to typically bring about loss of protein-free fluid fromthe blood to the bath, as in certain edematous conditions.

With hemofiltration, patients have fluid and waste products removed fromthe blood at a constant rate, twenty-four hours a day, for as long asnecessary, with the aid of a blood treatment device that comprises ahemofiltration cartridge. This technique is typically used on patientsfor whom hemodialysis is not considered safe, and also to treatconditions such as uremia, acute renal failure, refractory fluidoverload, and massive edema.

Embodiments of this invention that are provided with chambers 15 and 15′would in principle permit the puncturing of the corresponding graftvessels prior to the deflation of the corresponding balloons. However,as indicated above, occlusal balloons 60 and 60′ are preferably deflatedprior to the puncturing of the respective graft vessels 66 and 66′.Similarly, any puncturing device inserted through the walls of graftvessels 66 and 66′ is preferably removed prior to the distension of therespective occlusal balloons 60 and 60′.

When a treatment episode is completed, occlusal balloons 60 and 60′ arebrought back to their distended configurations by inflating them.Inflation is preferably achieved by injecting a fluid through therespective port devices 30 and 30′. These configurations of occlusalballoons 60 and 60′ prevent blood flow into the interior of graftvessels 66 and 66′, respectively. With the aid of the same needle thathas been used in the practice of hemodialysis or with a differentpuncturing device, the interior of graft vessels 66 and 66′ can bewashed and their contents replaced by a biocompatible fluid such asisotonic saline solution.

As indicated above, embodiments 5 and 5′ preferably remainsubcutaneously placed and ready to be accessed again in anothertreatment session. As also indicated in the foregoing description ofpreferred embodiments of this invention, blood flow in vessels 90 and90′ can preferably be exposed to an appropriate physiologically activeagent, such as heparin. This exposure is preferably provided during theperiods between hemodialysis sessions, so that the formation of bloodclots, or any other coagulation-related phenomenon, near the anastomosissites is significantly reduced.

As indicated in the foregoing description of preferred embodiments ofthis invention, embodiments 5 and 5′ can be additionally used tointravenously deliver medication while at least one of them isanastomosed, and this goal can be achieved too when both embodiments 5and 5′ are anastomosed for hemodialysis.

The sequence of steps related to the expansion/contraction of theocclusal balloons, the replacement of any fluid within graft vessels 66and 66′, and the optional intravenous delivery of medicine can beperformed according to the methods of this invention in any desiredbiocompatible order.

Examples of Use of Occlusal Balloons

FIGS. 9 and 10 show pressure and heparin transfer as a function of timeas experienced by an embodiment of a permeable balloon according to thepresent invention. In these experiments, solutions of heparin were usedat concentrations up to about 20000 IU. Solutions of albumin were usedat concentrations of up to about 5%. Commercial availability of therespective solutions of heparin and albumin determined the choice ofthese upper concentration limits.

Osmotic pressures were measured with a pressure transducer. The use ofthis device instead of liquid column height measurements reduces or evenavoids errors that are associated with the use of liquid columns. Theseerrors are typically associated with factors such as soluteconcentration inhomogeneity problems or frictional problems that canlead to incorrect pressure readings.

Solutions with heparin at different concentrations were used insuccessive experiments with embodiments of a permeable balloon. In someexperiments, the solutions contained albumin, whereas in otherexperiments no albumin was present. FIGS. 9 and 10 illustrate resultsobtained in experiments performed with a heparin solution with noalbumin (FIG. 9), and with a heparin solution with 1% albumin (FIG. 10).In embodiments with solutions that contained heparin only, the osmoticpressure is due to the heparin that remains in the balloon, whereas inembodiments with heparin and albumin solution, the osmotic pressure isdue to the albumin and to the heparin that remains in the balloon. Thedata shown in FIGS. 9 and 10 were obtained with Millipore 50 assemipermeable membrane, and with 20000 IU/ml heparin solutions.

As shown in FIG. 9, osmotic pressure of almost 80 mmHg was measuredshortly after the heparin solution was placed in a permeable balloon.The pressure remained above 80 mmHg for over 150 h, and remained at orabout 100 mmHg for at least 120 h. Heparin transfer rates were about 4IU ml⁻¹ h⁻¹ one day after the solution was placed in the balloon, andabout 7.7 IU ml⁻¹ h⁻¹ about 170 h after the solution was placed in theballoon.

FIG. 10 shows that a peak pressure of over 120 mmHg was obtained with asolution that contained heparin and 1% albumin. This observation shouldbe expected because in this case albumin, which does not significantlypermeate through the membrane, causes osmotic pressure in addition tothe heparin that remains within the balloon. Heparin transfer rates wereabout 5 IU ml⁻¹ h⁻¹ one day after the solution was placed in theballoon, and almost 9 IU ml⁻¹ h⁻¹ about 150 h after the solution wasplaced in the balloon.

These heparin transfer rates are adequate in light of desirabletransport rates in the range of about 5 IU ml⁻¹ h⁻¹ to about 10 IU ml⁻¹h⁻¹. These transport rates from a balloon whose volume is about 2 mllead to the intravenous administration of not more than 500 IU heparinper day, or to the administration of not more than 5000 IU heparin in aten-day period.

Safety measures, in addition to practical factors, determine thepreferred size of embodiments of permeable balloons of this invention.The administration of at most about 20000 IU heparin in a singleadministration is currently regarded as an acceptable risk. The amountof heparin that would be suddenly delivered upon rupture of a 5 mlballoon right after having been filled with heparin solution at aconcentration of 20000 IU/ml would be about 100000 IU. Instead, thisamount would be about 20000 IU if a 2 ml balloon were filled with 10000IU/ml heparin. Consequently, a 2-ml balloon is preferred in mostembodiments of permeable balloons.

The transport rates shown in FIGS. 9-10 also indicate each supply ofheparin within the balloon can intravenously provide heparin for atleast a ten-day period before the balloon is recharged with a freshsupply of heparin. The pressure data shown in the same Figures show thatsufficiently high pressure can be achieved with embodiments of thepresent invention because even in unusual conditions the venous pressuredoes not rise above 50 mmHg.

The foregoing procedure to determine osmotic pressure and concentrationsof substances in the fluid filling of an embodiment of an occlusalballoon according to this invention can be properly adapted withordinary skill in the art to analogously determine the osmotic pressureand adequate concentrations of other substances in the same or in adifferent type of vascular access.

SUMMARY OF PREFERRED EMBODIMENTS

The elements of the embodiments of this invention disclosed hereinabove,equivalents thereof, and their functionalities can be expressed as meansfor performing specified functions as described hereinbelow.

Many examples are provided herein of a means for selectively occludingan opening in a blood vessel. Examples of means for selectivelyoccluding an opening according to this invention include: occlusalballoons such as self-contained occlusal balloons, occlusal balloonswith a semipermeable membrane such as balloon 140 in FIG. 3, occlusalballoons with radio-opaque markings, occlusal balloons that are inflatedwith a liquid, occlusal balloons that are inflated with a gas, andocclusal balloons that are configured to operate in conjunction with orin the presence of at least another occlusal balloon, such as occlusalballoons 340, 341 in FIG. 5. Occlusal balloon 40 in FIG. 1 illustratesan exemplary embodiment of a self-contained occlusal balloon whendelivery end 42 does not essentially allow for significant mattertransport. Occlusal balloon 40 in FIG. 1 illustrates an exemplaryembodiment of an occlusal balloon with a semipermeable membrane whendelivery end 42 allows for selective matter transport.

Note that each embodiment of the means for selectively occluding anopening according to this invention has a delivery end that is generallylocated in the region near the anastomosis site and an opposite accessend that is typically provided with a connection to the means forselectively providing access to a means for selectively occluding anopening. Each embodiment of a means for selectively occluding an openingin a blood vessel functions according to this invention by adopting avariety of configurations such as a distended configuration and acontracted configuration. In particular, the distended configuration canbe an inflated configuration, and the contracted configuration can be acollapsed configuration. Preferably, the distended configuration isadopted when an embodiment of a means for selectively occluding anopening is filled with a liquid, although the fluid filling some of suchembodiments can also be a gas. Blood from the accessed vessel cannotinfiltrate into the anastomosed graft vessel when the embodiment of themeans for selectively occluding an opening is in its distendedconfiguration, whereas fluid communication from the interior of theanastomosed graft vessel into the lumen of the accessed blood vessel isallowed in the contracted configuration of the same embodiment. Any ofsuch specific embodiments is manufactured so that it can change from anyone of these particular configurations to the other and vice-versa aplurality of times. The number of times which these changes inconfiguration are experienced by embodiments of the means forselectively occluding an opening according to this invention can be ofthe order of the number of injections that a blood vessel wouldtypically be subjected to during a long term treatment of a chronicaffliction or during dialysis treatment.

Many examples are also provided herein of a means for selectivelyproviding access to a means for selectively occluding an opening in ablood vessel. Examples of means for selectively providing access to ameans for selectively occluding an opening in a blood vessel include:port devices such as a port device with one self-sealing access cavity,such as port devices 50 shown in FIG. 1 and port device 150 shown inFIGS. 2-3, a port device with a plurality of self-sealing accesscavities, such as port device 350 shown in FIG. 5, and a port devicethat includes ports for providing conduits to operate probes, samplingdevices, imaging devices and imaging device elements, or medicalintervention assisting devices.

Each embodiment of the means for selectively providing access to a meansfor selectively occluding an opening facilitates the externalintroduction into or the extraction from a specific embodiment of themeans for selectively occluding an opening of fluid therein contained.In particular, an embodiment of the means for selectively providingaccess to a means for selectively occluding an opening is adapted for asubcutaneous placement and it is provided with at least one self-sealingcavity for selectively allowing fluid communication through a conduitinto the access end of an embodiment of a means for selectivelyoccluding an opening in a blood vessel.

Examples are also provided herein of a means for selectively andcontrollably exposing blood flow to an agent in a vascular access. Meansfor selectively and controllably exposing blood flow to an agentaccording to this invention is embodied by means for selectivelyeffectuating transport of an agent in a vascular access, and by meansfor selectively subjecting blood flow to contact with an agent.Exemplary embodiments of each one of these means are enumerated in turnbelow.

Means for selectively effectuating transport of an agent in a vascularaccess according to this invention is embodied by permeating sources ofagents such as physiologically active agents. These permeating sourcesare more specifically embodied by sources such as a semipermeablemembrane, exemplified by semipermeable membranes 143 shown in FIG. 3,402 a shown in FIG. 6A, 402 b shown in FIG. 6B, 402 c shown in FIG. 6C,and 402 d shown in FIG. 6D; sources that include a plurality ofsemipermeable membranes, exemplified by semipermeable membranes 343 and345 shown in FIG. 5, semipermeable membranes in any of a mono-layer,bi-layer, tri- or generally multi-layer and sandwiched configurations;sources that include at least a semipermeable membrane with a backing(membrane mounting by backing); sources that include at least asemipermeable membrane braced to an embodiment of means for selectivelyoccluding an opening (membrane mounting by bracing), exemplified by theembodiment shown in FIG. 6C; sources that include at least asemipermeable membrane bonded to an embodiment of means for selectivelyoccluding an opening (membrane mounting by bonding), exemplified by theembodiment shown in FIG. 6B; sources that include at least asemipermeable membrane that is backed by material of an embodiment ofmeans for selectively occluding an opening (membrane mounting bybacking), exemplified by the embodiment shown in FIG. 6A; and sourcesthat include a semipermeable region of material of an embodiment ofmeans for selectively occluding an opening, exemplified by theembodiment shown in FIG. 6D.

Each embodiment of a means for selectively and controllably exposingblood flow to an agent in a vascular access is integrally formed in orattached to the delivery end of an embodiment of a means for selectivelyoccluding an opening according to this invention. The means forselectively and controllably exposing blood flow to an agent in avascular access functions according to the present invention by exposingthe blood flow at the anastomosis site to at least one physiologicallyactive agent, such as a substance that will prevent the formation ofblood clots. Means for selectively and controllably subjecting bloodflow to contact with an agent according to this invention is embodied byin-situ sources of physiologically active agents and by nonpermeatingsources of physiologically active agents.

The anastomosed graft of this invention provides physical support to aparticular embodiment of the means for selectively occluding an openingand to a particular embodiment of the means for selectively providingaccess to a means for selectively occluding an opening. In preferredembodiments, this support is provided by a housing such that theanastomosed graft contains in its interior an embodiment of a means forselectively occluding an opening which has attached thereto anembodiment of a means for selectively exposing blood flow to an agent inthe vascular access.

One of the ends of the anastomosed graft of this invention isanastomosed to the vessel being accessed. The opposite end of theanastomosed graft is integrally or detachably connected to an embodimentof means for providing access to a means for selectively occluding anopening.

The present invention may be embodied in other specific forms withoutdeparting from its spirit or essential characteristics. The describedembodiments are to be considered in all respects only as illustrativeand not restrictive. The scope of the invention is, therefore, indicatedby the appended claims rather than by the foregoing description. Allchanges which come within the meaning and range of equivalency of theclaims are to be embraced within their scope.

What is claimed and desired to be secured by United States LettersPatent is:
 1. A method for external treatment of blood, comprising:providing an occludable extraction graft vessel having an anastomosisend which is anastomosed to an extraction blood vessel, wherein theextraction graft vessel is occluded at its anastomosis end to preventblood from entering the occludable extraction graft vessel; providing anoccludable delivery graft vessel having an anastomosis end which isanastomosed to a delivery blood vessel, wherein the occludable deliverygraft vessel is occluded at its anastomosis end to prevent blood fromentering the occludable delivery graft vessel; enabling fluidcommunication between said extraction blood vessel and said occludableextraction graft vessel; enabling fluid communication between saiddelivery blood vessel and said occludable delivery graft vessel;allowing blood to flow in fluid communication between said occludableextraction graft vessel to a blood treatment device and then to saiddelivery graft vessel, such that blood flow from said occludableextraction graft vessel first reaches said blood treatment device andthen reaches said occludable delivery graft vessel after being treated;and occluding said occludable extraction graft vessel and saidoccludable delivery graft vessel at their respective anastomosis endsafter completion of blood treatment with the blood treatment device. 2.The method as recited in claim 1, wherein said extraction blood vesselis an artery and said delivery blood vessel is a vein.
 3. The method asrecited in claim 1, wherein said extraction blood vessel is a vein andsaid delivery blood vessel is a vein.
 4. The method as recited in claim1, wherein at least one of said occludable extraction graft vessel andsaid occludable delivery graft vessel is configured for the delivery ofa physiologically active agent into the blood.
 5. The method as recitedin claim 1, wherein at least one of said occludable extraction graftvessel and said occludable delivery graft vessel is configured for thedelivery of heparin into the blood.
 6. The method as recited in claim 1,wherein said blood treatment device is a hemodialyzer.
 7. The method asrecited in claim 1, wherein said blood treatment device is aplasmapheresis separator.
 8. The method as recited in claim 1, whereinsaid blood treatment device is an ultrafiltration hemodialyzer.
 9. Themethod as recited in claim 1, wherein said blood treatment devicecomprises a biocompatible hemoperfusion cartridge for hemoperfusion. 10.The method as recited in claim 1, wherein said blood treatment devicecomprises a hemofiltration cartridge.
 11. A method for externaltreatment of blood, comprising: providing an occludable extraction graftvessel having an anastomosis end which is anastomosed to an extractionblood vessel, wherein the occludable extraction graft vessel is occudedat its anastomosis end to prevent blood from entering the occludableextraction graft vessel; providing an occludable delivery graft vesselhaving an anastomosis end which is anastomosed to a delivery bloodvessel, wherein the occludable delivery graft vessel is occluded at itsanastomosis end to prevent blood from entering the occludable deliverygraft vessel; enabling fluid communication between said extraction bloodvessel and said occludable extraction graft vessel; enabling fluidcommunication between said delivery blood vessel and said occludabledelivery graft vessel; accessing said occludable extraction graftvessel; accessing said occludable delivery graft vessel; establishingfluid communication from said occludable extraction graft vessel to saidoccludable delivery graft vessel via a blood treatment device to enableblood flowing from said occludable extraction graft vessel to be treatedby said blood treatment device and then to be returned into saidoccludable delivery graft vessel; and occluding said occludableextraction graft vessel and said occludable delivery graft vessel attheir respective anastomosis ends after completion of blood treatmentwith the blood treatment device.
 12. The method as recited in claim 11,wherein said extraction blood vessel is an artery and said deliveryblood vessel is a vein.
 13. The method as recited in claim 11, whereinsaid extraction blood vessel is a vein and said delivery blood vessel isa vein.
 14. The method as recited in claim 11, wherein at least one ofsaid occludable extraction graft vessel and said occludable deliverygraft vessel is configured for the delivery of a physiologically activeagent into the blood.
 15. The method as recited in claim 11, wherein atleast one of said occludable extraction graft vessel and said occludabledelivery graft vessel is configured for the delivery of heparin into theblood.
 16. The method as recited in claim 11, wherein said step ofenabling fluid communication between said extraction blood vessel andsaid occludable extraction graft vessel is achieved by deflating anocclusal balloon positioned in said occludable extraction graft vessel.17. The method as recited in claim 11, wherein said step of enablingfluid communication between said delivery blood vessel and saidoccludable delivery graft vessel is achieved by deflating an occlusalballoon positioned in said occludable delivery graft vessel.
 18. Themethod as recited in claim 16, further comprising expanding saidocclusal balloon after the external treatment of the blood such thatsaid occludable extraction graft vessel is effectively sealed at itsanastomosis end.
 19. The method as recited in claim 17, furthercomprising expanding said occlusal balloon after the external treatmentof the blood such that said occludable delivery graft vessel iseffectively sealed at its anastomosis end.
 20. The method as recited inclaim 11, wherein said blood treatment device is a hemodialyzer.
 21. Amethod for external treatment of blood, comprising: providing anoccludable extraction graft vessel having an anastomosis end which isanastomosed to an extraction blood vessel, the occludable extractiongraft vessel having an occlusal balloon disposed herein; providing anoccludable delivery graft vessel having an anastomosis end which isanastomosed to a delivery blood vessel, the occludable delivery graftvessel having an occlusal balloon disposed therein, wherein theoccludable extraction graft vessel and the occludable delivery graftvessel are distinct vessels; enabling fluid communication between saidextraction blood vessel and said occludable extraction graft vessel bydeflating the occlusal balloon in the occludable extraction graftvessel; enabling fluid communication between said delivery blood vesseland said occludable delivery graft vessel by deflating the occlusalballoon in the occludable delivery graft vessel; accessing saidoccludable extraction graft vessel; accessing said occludable deliverygraft vessel; and establishing fluid communication from said occludableextraction graft vessel to said occludable delivery graft vessel via ablood treatment device to enable blood flowing from said occludableextraction graft vessel to be treated by said blood treatment device andthen to be returned into said occludable delivery graft vessel.
 22. Themethod as recited in claim 21, wherein said extraction blood vessel isan artery and said delivery blood vessel is a vein.
 23. The method asrecited in claim 21, wherein said extraction blood vessel is a vein andsaid delivery blood vessel is a vein.
 24. The method as recited in claim21, wherein at least one of the occlusal balloons is configured for thedelivery of a physiologically active agent into the blood.
 25. Themethod as recited in claim 21, wherein at least one of said occlusalballoons is configured for the delivery of heparin into the blood. 26.The method as recited in claim 21, wherein said blood treatment deviceis a hemodialyzer.
 27. The method as recited in claim 21, furthercomprising the step of terminating fluid communication between saidoccludable extraction graft vessel, said blood treatment device and saidoccludable delivery graft vessel by expanding at least one of theocclusal balloons after the external treatment of the blood.
 28. Amethod for external treatment of blood, comprising: providing anoccludable extraction graft vessel having an anastomosis end which isanastomosed to an extraction blood vessel, the occludable extractiongraft vessel having an occlusal balloon disposed therein; providing anoccludable delivery graft vessel having an anastomosis end which isanastomosed to a delivery blood vessel, the occludable delivery graftvessel having an occlusal balloon disposed therein; enabling fluidcommunication between said extraction blood vessel and said occludableextraction graft vessel by deflating the occlusal balloon in theoccludable extraction graft vessel; enabling fluid communication betweensaid delivery blood vessel and said occludable delivery graft vessel bydeflating the occlusal balloon in the occludable delivery graft vessel;accessing said occludable extraction graft vessel; accessing saidoccludable delivery graft vessel; establishing fluid communication fromsaid occludable extraction graft vessel to said occludable deliverygraft vessel via a blood treatment device to enable blood flowing fromsaid occludable extraction graft vessel to be treated by said bloodtreatment device and then to be returned into said occludable deliverygraft vessel; and terminating fluid communication between saidoccludable extraction graft vessel, said blood treatment device and saidoccludable delivery graft vessel by expanding at least one of theocclusal balloons upon completion of the treatment of the blood.
 29. Ahemodialysis method, comprising: providing an occludable extractiongraft vessel having an anastomosis end which is anastomosed to anextraction blood vessel, the occludable extraction graft vessel havingan occlusal balloon disposed therein; providing an occludable deliverygraft vessel having an anastomosis end which is anastomosed to adelivery blood vessel, the occludable delivery graft vessel having anocclusal balloon disposed therein, wherein the occludable extractiongraft vessel and the occludable delivery graft vessel are distinctvessels; enabling fluid communication between said extraction bloodvessel and said occludable extraction graft vessel by deflating theocclusal balloon in the occludable extraction graft vessel; enablingfluid communication between said delivery blood vessel and saidoccludable delivery graft vessel by deflating the occlusal balloon inthe occludable delivery graft vessel; accessing said occludableextraction graft vessel; accessing said occludable delivery graftvessel; and establishing fluid communication from said occludableextraction graft vessel to said occludable delivery graft vessel via ahemodialyzer to enable blood flowing from said occludable extractiongraft vessel to be treated by said hemodialyzer and then to be returnedinto said occludable delivery graft vessel.
 30. The method as recited inclaim 29, wherein said extraction blood vessel is an artery and saiddelivery blood vessel is a vein.
 31. The method as recited in claim 29,wherein said extraction blood vessel is a vein and said delivery bloodvessel is a vein.
 32. The method as recited in claim 29, wherein atleast one of the occlusal balloons is configured for the delivery of aphysiologically active agent into the blood.
 33. The method as recitedin claim 29, wherein at least one of said occlusal balloons isconfigured for the delivery of heparin into the blood.
 34. The method asrecited in claim 29, further comprising terminating fluid communicationbetween said occludable extraction graft vessel, said hemodialyzer andsaid occludable delivery graft vessel by expanding at least one of theocclusal balloons upon completion of the treatment of the blood.